DESCRIPTION:(from applicant's abstract) The role that a neuron plays in a neural network is shaped by its intrinsic excitability, which is established developmentally to co-ordinate with its function within that network. We will study the control of neuronal firing properties in the rat peripheral sympathetic nervous system. There are two types of neurons in this system. Neurons in paravertebral ganglia have a simple wiring diagram and synaptic input to these cells is dominated by a large suprathreshold input from a single preganglionic motor neuron. These cells strongly accommodate in response to a sustained depolarizing current and are known as phasic neurons. In contrast, neurons in prevertebral ganglia integrate multiple small synaptic inputs from both sensory and motor neurons. These cells fire repetitively in response to a sustained depolarizing current and are known as tonic neurons. These different firing properties are determined by the differential expression of specific potassium currents. Phasic firing is produced by expression of a relatively large M-current. Tonic firing properties correlate with expression of an inward rectifier current and a low threshold, slowly inactivating current known as a D2 current. These two distinct electrophysiological phenotypes are determined during development by inductive events that affect transcriptional regulation of potassium channel genes. The overall aim of this proposal is to determine the molecular identity of those currents that control the switch in firing properties and to understand how the regulation of these channels is achieved. This work has relevance to the study of epilepsy since the regulation of intrinsic neuronal excitability is a key factor in determining the overall excitability of a neural network.